In the late 1950s and early ’60s, Dr. Emil Frei III joined with colleagues at the National Cancer Institute to pioneer combining different kinds of chemotherapy to treat children with acute lymphocytic leukemia.

At a time when the diagnosis was a death sentence for most children, the experimental treatments he and his colleagues devised cured many patients. Their research in subsequent years led to more effective treatments for other forms of cancer in children and adults.

As adept at the bedside as in a laboratory, Dr. Frei approached all his work with optimism and warmth that inspired researchers and patients alike.

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“Dr. Frei was a giant in the field of pediatric oncology and was a world-class researcher,” said Edward M. Kennedy Jr., who went to see Dr. Frei in the early 1970s after being diagnosed with osteosarcoma. “Of course I, as a 12-year-old boy under his care, knew him as an amazing healer who was really able to look beyond the disease, beyond the tumor, at the whole person. I think that was really what made him unique. Despite his stature and reputation and professional accolades, he was a remarkably humble man.”

Dr. Frei, who formerly was physician-in-chief and director of Dana-Farber Cancer Institute, which he led during a time of steady expansion, died Tuesday in his daughter’s home in Oak Park, Ill. He was 89 and his health had declined rapidly over the past couple of weeks.

Dr. David Nathan, former president of Dana-Farber, said in a statement that Dr. Frei “was one of a handful of physicians who developed combination chemotherapy for cancer and produced the first cures of childhood leukemia.”

Physicians including Dr. Frei and his longtime friend and colleague Dr. Emil Freireich could measure their success in the lives they extended long beyond a devastating diagnosis. At a press conference after an award ceremony in the mid-1980s, a woman approached Dr. Frei, he recalled in a 1997 interview as part of the National Cancer Institute Oral History Project.

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She mentioned her name “and of course I knew her immediately. She was 7 years old when we had treated her at NCI,” Dr. Frei told interviewer Gretchen Case. “This was something like 20 years later. She was the mother of two children. We hugged and I told her that this was what it was all about. It’s a life and death situation here thrown together.”

“Dr. Frei and his colleagues saved the lives of literally millions of cancer patients by championing the then novel idea of combination chemotherapy for cancer over 40 years ago, and then developing effective combination regimens for previously incurable cancers,” Dr. Edward J. Benz Jr., Dana-Farber’s president, said in a statement.

“The majority of patients with certain forms of childhood leukemia, Hodgkin disease, testicular cancer, and some other cancers can now expect to live long and high-quality lives because of his contributions,” Benz added.

He also praised Dr. Frei’s leadership at Dana-Farber. Within several years of when Dr. Frei arrived in 1972 and succeeded Dr. Sidney Farber, the founder, as physician-in-chief, the staff increased from 150 to 900.

Dr. Harold Varmus, director of the National Cancer Institute, said that Dr. Frei “understood the importance of combining therapies. Using that general approach turned the very rare successes in treating childhood leukemias into very frequent successes.”

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In addition, Varmus said, Dr. Frei’s work designing clinical trials “and his high standards for clinical research … set a standard that we’ve been trying to emulate ever since.”

Born in St. Louis, Dr. Frei grew up in a family known for its stained-glass business.

“I went into science; the rest of them are artists,” he told the St. Louis Post-Dispatch in 1999, calling himself the “black sheep” of the family.

As a teenager, he was inspired to seek a career outside the family business after reading Harvard bacteriologist Hans Zinsser’s book “Rats, Lice and History.”

During World War II, he served in the Navy, which sent him to study at Colgate University in Hamilton, N.Y. He then went to Yale University’s School of Medicine and graduated in 1948.

After returning to St. Louis for his internship and residency, he served as an officer in the Navy Medical Corps in Korea during the Korean War.

In 1948, Dr. Frei married Elizabeth Smith, with whom he had five children. She died in 1986.

His second wife, the former Adoria Smetana Brock, died in 2009.

Dr. Frei’s son, Emil IV of Andover, recalled accompanying his father on hospital rounds and watching him interact with patients.

“He would sit at the side of the bed, touch their hand, talk to them in a compassionate, warm way,” his son said. “What I remember most was his ability to connect with patients, which I thought was really extraordinary.”

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As a father, Dr. Frei “had an optimism that was just absolutely contagious,” his son said. “And he always had a deep and abiding respect for education. It wasn’t that it conferred degrees or accolades. People who pursued education were expressing interest in exploring a wider world than the world they lived in.”

He added that his father “was more curious than any human being I’ve ever run into.”

Much of Dr. Frei’s groundbreaking work had its roots in the decade he spent at the National Cancer Institute, beginning in the mid-1950s. In 1965, he went to the M.D. Anderson Cancer Center in Houston, where he was associate scientific director of clinical research and chairman of the department of experimental therapeutics.

Dr. Frei, who was known as Tom, also taught at Harvard Medical School during his years at Dana-Farber. Often was honored for his work, including with the 1972 Albert Lasker Clinical Medical Research Award
for his contributions in combination chemotherapy.

A service will be announced for Dr. Frei, who in addition to his son leaves four daughters, Mary of Bedford Hills, N.Y., Alice of Houston, Nancy of Alaska, and Judy of Oak Park, Ill.; a brother, Bob of St. Louis; and 10 grandchildren.

In 1987, Dr. Frei surveyed a gathering of cancer survivors and their families at Dana-Farber and told them that “a lot of people still think that cancer equals death. Your presence here is tangible evidence that that’s not so.”

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Because of his ability to “connect in an emotional way with the patient,” Kennedy said, “I actually looked forward to my appointments with Dr. Frei. I honestly believe that Dr. Frei saved my life. I also know he saved the lives of thousands of other pediatric cancer patients.”